A solid pharmaceutical composition or dosage form, such as a tablet or capsule, is generally composed of a mixture of active ingredient(s) and excipient(s). The reproducibility of the adsorption of an active ingredient (drug) from a solid composition form after oral administration depends on several factors such as the release of the drug from the composition and the dissolution or solubilization of the drug under physiological conditions. Because of the critical nature of the release of the drug from the composition and the dissolution or solubilization of the drug, a dissolution test is highly relevant to the prediction of the in vivo performance of a drug. Drug approving authorities such as the FDA and EMA often require pharmaceutical companies to determine the drug release characteristics of any new pharmaceutical composition in order to obtain approval. These tests can also be required as an USP quality parameter, to assess batch-to-batch quality of a pharmaceutical composition, for accepting products, waiving bioequivalence requirements or supporting requests for other bioequivalence requirements than the recommended.
Various protocols have been developed for conducting the in vitro dissolution tests and are routinely applied for both product development and quality control. Drug dissolution testing is mostly conducted using recommended compendia methods and apparatus, such as the U.S. Pharmacopoeia and the European Pharmacopoeia e.g. USP 34 <711> and EP 7.2, 2.9.3. The FDA website provides extensive information on existing dissolution methods, and its contents are herein incorporated by reference in its entirety.
Dissolution media typically used in such tests are for example water and buffers such as phosphate buffers or citrate buffers. Different types of dissolution apparatus, based on different agitation methods are available commercially and are recognized by the compendia methods. These apparatus include: paddle, basket, flow-through, and reciprocating cylinder. While exact procedures (protocols) and apparatus vary, all drug dissolution test methods involve placing the pharmaceutical composition or dosage form into a dissolution medium and applying some agitation to the dissolution medium in order to promote disintegration and dissolution of the drug under test.
The dissolution medium and the detection method for determining the amount of the released drug in the dissolution medium depends upon (is chosen according) the chemical nature of the drug, and physical and stability considerations are also of great importance in making the appropriate choices.
Currently, there is no effective dissolution test for measuring the amount of API such as ivermectin with or without pyrantel in chewable, complex matrix, dosage forms. Moreover, the inventors are aware of no effective methods for measuring the amount of any hydrophobic API distributed in a similarly complex dosage form (e.g. medicated pet treats and the like). Finally, more and more API are being delivered to companion animals, including dogs and cats, in “treat form.” Accordingly, there is a long-felt need to establish an effective dissolution method useful in dissolving complex matrix dosage forms for the subsequent quantification of APIs.